Interleukin-1 signaling contributes to endurance training-induced skeletal muscle adaptations.

Abstract

Interleukin (IL)-1 is widely recognized as an inflammatory cytokine induced in response to muscle injury, where it contributes to the clearance of damaged fibers and supports subsequent regenerative and reparative processes. In contrast, IL-1 derived from infiltrating neutrophils in response to transient, nondamaging exercise has been reported to regulate energy metabolism during endurance exercise. Therefore, in the present study, we investigated the role of IL-1 in skeletal muscle endurance adaptations induced by chronic endurance training (ET). Thirteen-week-old BALB/c wild-type (WT) mice and mice deficient in both IL-1α and IL-1β [IL-1 knockout (KO); IL-1 KO] were used. The left hindlimb was subjected to ET induced by electrical stimulation of the triceps surae muscle three times per week for 5 wk, whereas the right hindlimb served as a control. Baseline muscle endurance did not differ between WT and IL-1 KO mice. Following ET, muscle endurance and mitochondrial respiration were significantly increased in WT mice but not in IL-1 KO mice. Moreover, ET induced increases in citrate synthase activity and the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), mitochondrial respiratory chain complexes I and III, and hexokinase 2 exclusively in WT mice. A single bout of exercise significantly increased IL-1β mRNA, but not IL-1α mRNA, in WT mice. In addition, exercise-induced phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and increases in PGC-1α-b and hexokinase 2 mRNA expression were attenuated in IL-1 KO mice. These findings suggest that IL-1 signaling is associated with ET-induced improvements in muscle endurance and mitochondrial quantity and quality, possibly through activation of the p38 MAPK pathway.NEW & NOTEWORTHY Interleukin (IL)-1 is widely recognized as an injury-associated inflammatory cytokine in skeletal muscle, and inflammation is generally considered detrimental to muscle function. Here, we provide evidence that IL-1 signaling contributes to endurance training-induced muscle adaptation. Using IL-1α/β-deficient mice, we show that loss of IL-1 attenuates training-induced improvements in muscle endurance and mitochondrial remodeling, which may be associated with altered activation of the p38 MAPK signaling following acute endurance exercise.